We propose to continue a broadly based multidisciplinary approach to the study of hemostasis and thrombosis. Platelet receptors will be studied by advanced microscopic techniques including video- enhanced light microscopy, high resolution low voltage scanning electron microscopy, and high voltage transmission electron microscopy. Particular attention will be paid to the movement of platelet receptors during platelet activation. The role of platelets in arterial thrombosis and embolization will be investigated in animal models. Particular attention will be paid to validation of these models for studies of antithrombotic agents and new imaging techniques. The structure and function of two interesting heparin-binding proteins, thrombospondin and vitronectin, will be investigated, particularly in regard to the interactions of these proteins with cells, glycosaminoglycans, other matrix molecules, and proteins of the coagulation system. The metabolism and action of vitamin K will be studied in experimental animals and man. Particular attention will be paid to the condition of borderline vitamin K deficiency. An administrative and clinical core will expedite interactions of the Program Project with interested parties on the University of Wisconsin-Madison Campus and development of protocols for the study of patients.